Primary central nervous system (CNS) tumors are associated with dismal outcome and very poor survival rates. Comprehensive genomic profiling (CGP) approaches may contribute to the deeper understanding of the pathogenesis of these entities and can be harnessed to reveal potential therapeutic targets and offer personalized treatment options in patients with CNS tumors.
Diagnostic samples of 42 patients with primary CNS tumors were investigated using Illumina TruSight Oncology 500 assay. Single nucleotide variants (SNV), small insertions and deletions, copy number alterations and gene fusions were analyzed along with microsatellite instability status and the tumor mutation burden. Actionable variants were determined using the Qiagen Clinical Insight and PierianDx software.
Potentially targetable genomic alterations were identified in 69.0% (29/42) of the patients. Pathogenic SNVs, insertions and deletions were detected in 66.7% (28/42) of the patients with TP53, NTRK3 and FAT1 genes representing the most frequently affected loci. Twenty gene amplifications (copy number > 5) were uncovered in 19.0% patients, with MYC, PDGFRA and KIT genes being the most frequently revealed alterations. Gene fusions were detected in 10 (23.8%) patients. BRAF fusions, ETV5-DGKG translocations (4.4%), and NTRK3 fusions were detected in 9.5%, 4.4% and 2.4% of the cases, respectively. NGS revealed a novel BRAF::PID1gene fusion in a sample diagnosed with pilocytic astrocytoma. All but one patient was characterized by low tumor mutational burden and none of the analyzed patients displayed microsatellite-instability. Eleven patients (26.2%) have received targeted therapy based on their molecular profile. Trametinib, dasatinib and cabozantinib were the most commonly used agents. Partial remission or stable disease has been observed in patients receiving targeted therapies for at least 6 months.
In our study, routine application of the Illumina TruSight Oncology 500 CPG approach led to the identification of targetable alterations in 69.0% of the patients with 26.2% of the patients receiving targeted therapy.
C. Bödör and M. Garami.
EU Horizon 2020 - 739593, TKP2021-EGA-24, TKP2021-NVA-15, EFOP-3.6.3-VEKOP-16-2017-00009 grants.
O. Brzon: Non-Financial Interests, Institutional, Full or part-time Employment: Institute of Applied Biotechnologies Inc. All other authors have declared no conflicts of interest.